Resistance to mesenchymal reprogramming sustains clonal propagation in metastatic breast cancer

The acquisition of mesenchymal traits is considered a hallmark of breast cancer progression. However, the functional relevance of epithelial-to-mesenchymal transition (EMT) remains controversial and context dependent. Here, we isolate epithelial and mesenchymal populations from human breast cancer metastatic biopsies and assess their functional potential in vivo. Strikingly, progressively decreasing epithelial cell adhesion molecule (EPCAM) levels correlate with declining disease propagation. Mechanistically, we find that persistent EPCAM expression marks epithelial clones that resist EMT induction and propagate competitively. In contrast, loss of EPCAM defines clones arrested in a mesenchymal state, with concomitant suppression of tumorigenicity and metastatic potential. This dichotomy results from distinct clonal trajectories impacting global epigenetic programs that are determined by the interplay between human ZEB1 and its target GRHL2. Collectively, our results indicate that susceptibility to irreversible EMT restrains clonal propagation, whereas resistance to mesenchymal reprogramming sustains disease spread in multiple models of human metastatic breast cancer, including patient-derived cells in vivo

How Perceived Causal Networks (PECAN) can complement case conceptualization, diagnostic classification and data-based networks: An introduction to a method for constructing personalized networks

The personalization of psychopathology through the use of personalized symptom networks appears to be a promising approach for gaining deeper insights into the development and maintenance of mental disorders and for improving psychotherapy. One way to create such networks is by using the PErceived CAusal Networks (PECAN) method. In this method, respondents are systematically asked to quantify how their symptoms are causally linked. Answers are then visualized, either for the individual or aggregated for a group, as a directed network. As compared to time-series analysis, the more established method to create personalized networks, PECAN can represent causal relations irrespective of their time-scales and requiring no data-heavy estimations. The following guidelines are intended to assist clinicians and researchers in the creation of personalized networks using the PECAN method. These networks can facilitate case conceptualization and personalization of treatments for individual patients and the description of groups of patients, thereby revealing recurring feedback loops and consistently central symptoms. Additionally, recommendations are provided regarding the procedures to be employed in the selection of nodes, assessment of edges, and visualization of the data. Furthermore, the potential for evaluating the reliability, validity, clinical usefulness as well as strength, limitations and future challenges of PECAN are discussed. We conclude with an overview of the challenges of PECAN and a research agenda that highlights opportunities to improve the still very young method and implement it in clinical research and practice

Development of the CMS detector for the CERN LHC Run 3

International audienceSince the initial data taking of the CERN LHC, the CMS experiment has undergone substantial upgrades and improvements. This paper discusses the CMS detector as it is configured for the third data-taking period of the CERN LHC, Run 3, which started in 2022. The entire silicon pixel tracking detector was replaced. A new powering system for the superconducting solenoid was installed. The electronics of the hadron calorimeter was upgraded. All the muon electronic systems were upgraded, and new muon detector stations were added, including a gas electron multiplier detector. The precision proton spectrometer was upgraded. The dedicated luminosity detectors and the beam loss monitor were refurbished. Substantial improvements to the trigger, data acquisition, software, and computing systems were also implemented, including a new hybrid CPU/GPU farm for the high-level trigger

Measurement of the τ\tau lepton polarization in Z boson decays in proton-proton collisions at s\sqrt{s} = 13 TeV

International audienceThe polarization of $\tau$ leptons is measured using leptonic and hadronic $\tau$ lepton decays in Z $\to\tau^+\tau^-$ events in proton-proton collisions at $\sqrt{s}$ = 13 TeV recorded by CMS at the CERN LHC with an integrated luminosity of 36.3 fb$^{-1}$. The measured $\tau^-$ polarization at the Z boson mass pole is $\mathcal{P}_{\tau}$(Z) = $-$0.144$\pm$0.006 (stat) $\pm$ 0.014 (syst) = $-$0.144$\pm$0.015, in good agreement with the measurement of the $\tau$ lepton asymmetry parameter of $A_{\tau}$ = 0.1439$\pm$0.0043 = $-\mathcal{P}_{\tau}$(Z) at LEP. The $\tau$ polarization depends on the ratio of the vector to axial-vector couplings of the $\tau$ leptons in the neutral current expression, and thus on the effective weak mixing angle $\sin^{2}\theta_\mathrm{W}^{\text{eff}}$, independently of the Z boson production mechanism. The obtained value $\sin^{2}\theta_\mathrm{W}^{\text{eff}}$ = 0.2319$\pm$0.0008 (stat) $\pm$ 0.0018 (syst) = 0.2319$\pm$0.0019 is in good agreement with measurements at e$^+$e$^-$ colliders